The major histocompatibility complex (MHC) of the mouse controls a number of immunologically related functions. The immune response of individuals and inbred strains to a wide variety of synthetic and natural antigens is controlled by dominant genes that map within the I region of the MHC, and have been termed histocompatibility or H-linked Ir genes. The I region also codes for a series of cell surface (Ia) antigens. A number of experiments suggest that Ir genes exert their effect via cell interactions mediated by Ia alloantigenic molecules. With the goal of elucidating the molecular basis by which Ia alloantigens mediate their functions, we propose to subject them to detailed structural studies. We will employ microsequencing methods that have recently been developed, and which have previously been successfully applied to the structural analysis of the H-2K and H-2D gene products. Such studies may provide a framework for correlating the structure of these molecules with their functions.